Brexpiprazole (Brexpiprazole, Code: OPC-34712) is a new generation of anti-psychotic drug candidates developed by Otsuka Pharmaceutical Co., Ltd., it takes effect on several receptors, i.e., it is the dopamine D2 receptor partial agonist (improving positive and negative symptoms, cognitive disorder and depressive symptoms), 5-HT2A receptor antagonist (improving negative symptoms, cognitive function disorder, symptoms of depression, insomnia), al adrenergic receptor antagonists (improving the positive symptoms of schizophrenia), 5-hydroxytryptamine uptake/reuptake inhibitors (improving depressive symptoms), a 5-HT1A partial agonist (having anxiolytic and antidepressant activity) and 5-HT7 antagonists (adjusting body temperature, circadian rhythm, learning and memory, sleep) at the same time. Currently, a Phase III clinical trial for adjuvant treatment of severe depression (MIDD) is conducted in the United States and Europe; a Phase III clinical trial for the treatment of schizophrenia is conducted in the United States, Europe and Japan; meanwhile, a Phase II clinical trial for Adult ADHD (attention deficit hyperactivity disorder) is conducted in the United States.
A preparation route of brexpiprazole is disclosed in the PCT application WO2006112464 A1 by Otsuka Pharmaceutical Co., Ltd. as shown in Scheme 1, the disadvantage of this route is that by-products that cannot be easily separated are produced in the first step of the reaction, intermediates with high purity cannot be easily obtained even by column chromatography. Thus it suffered from reduced purity and yield of the final product brexpiprazole.

Then, another preparation route of this reaction is disclosed in the PCT application WO2013015456 A1 by Otsuka Pharmaceutical Co., Ltd. as shown in Scheme 2, the reagents used in the route are relatively expensive, so the disadvantage of the route is costly, environmentally unfriendly and not suitable for industrial production.

There are disadvantages of highcost, formation of impurities hard to separate for the above preparation method. Thus it is necessary to find a new route which is economic, practical and environmentally friendly, so as to improve process stability, reduce the cost and improve the product quality.